Significance Although non-primate lentiviruses have never been observed to infect primates,recent studies suggest that a lentivirus that infects goats, caprine arthritis encephalitis virus (CAEV), may also infect humans. Because cross-species transmission of primate lentiviruses is thought to account for the evolution of human immunodeficiency virus (HIV), it is important to evaluate the potential for transmission of non-primate lentiviruses to humans or other primates. Objectives Infection of rhesus macaques with simian immunodeficiency virus is a well-established model for primate lentiviral infection and disease pathogenesis. This study was done to determine if rhesus macaques inoculated with blood from a human patient with arthritis and apparently infected with a novel CAEV would develop persistent CAEV infection or disease. Results About 6 months after intravenous inoculation of one adult rhesus macaque with 10 ml of human blood, a virus-specific polymerase chain reaction (PCR) assay detected CAEV proviral genome in DNA extracted from the animal[unreadable]s peripheral blood mononuclear cells. Although the monkey remains seronegative against a goat CAEV strain, it has not yet been determined if the animal[unreadable]s serum reacts to the human isolate with which it was inoculated. No efforts have been made as yet to culture virus from the macaque[unreadable]s blood. No clinical signs of disease or any abnormalities in peripheral blood characteristics were observed during the study period of 10 months. Thus, although there is no proof that the inoculated macaque is infected, definitive studies to address this issue are pending. Future Directions Studies will be performed to (a) identify the cells in blood that carry the proviral genome detected by PCR, (b) estimate the number of infected blood cells, (c) test monkey serum for reactivity to human CAEV. Additional rhesus macaques will be inoculated with blood from other people infected with CAEV variants or with the goat CAEV. KEYWORDS lentivirus, CAEV, arthritis